SAMe S-adenosylmethionine for Depression and Neuroprotection Richard P. Brown MD Associate Professor of Clinical Psychiatry Columbia University College of Physicians and Surgeons

Presenter Disclosures Richard P. Brown, MD The following personal financial relationships with commercial interests relevant to this presentation existed during the past 12 months: No relationships to disclose.

“You’ve been fooling around with alternative medicines, haven’t you?”

SAMe physiological compound ranks with ATP as pivotal molecule SAMe: distributed all tissues and fluids of the body and fundamental to > 100 biochemical reactions (Adapted from Peter W Billigman)

Metabolism of SAMe Methylation Amino-propylation SAM-e Produces: Serotonin Norepinephrine Dopamine DNA, proteins Phospholipids x Amino-propylation x-CH3 SAM-e Joint Health SAH deca-Sam-e PPi Putrescine Spermidine Trans-sulfuration Spermidine Spermine ATP MTA Homocysteine (Hcy) Cystathionine B12 Methionine Cysteine MTHF (THF) Terahydrofolate sulfate (S04) Glutathione (GSH) Major Antioxidant

SAMe Is an Effective Anti-Depressant 12/13 studies – SAMe improved depression significantly more than placebo (1 negative study had flawed procedures) 19 DBRCTs - SAMe improved depression significantly more than tricyclic antidepressants Augmented effects of other antidepressants Increased response and remission in 73 SSRI nonresponders (Berlanga C, et al. 1992; Papakostas et al. Am J Psych 2010;167:942-948)

What is the # 1 Misconception about SAMe? Same increases homocysteine, a risk factor associated with cardiovascular disease. True False X

SAMe Does NOT Increase Homocysteine Mayo Clinic DBRPC 52 healthy adults given placebo or SAMe (800mg/day) for 4 weeks No significant change in plasma Homocysteine (Thompson MA, et al. 2009. Dietary supplement S-adenosyl-L-methionine (AdoMet) effects on plasma homocysteine levels in healthy subjects: a double-blind, placebo-controlled, randomized clinical trial. JACM 15(5): 523-9)

SAMe: Clinical Benefits Endogenous depression  augment response to Rx antidepressants Depression in people with Parkinson's, fibromyalgia, rheumatoid arthritis, HIV Improve liver function in hepatitis, cirrhosis Cognitive function Attention Deficit Disorder Pain of fibromyalgia Opiate and alcohol withdrawal

What is the # 2 Misconception about SAMe? “People with Parkinson’s Disease should not take SAMe” True False X

This misconception stems from a study in which a solution of SAMe was injected into the ventricles in the brains of rats. The injection adversely affected the neurons resulting in tremors that were seen as similar to tremors in Parkinson’s disease (PD) . Such an effect has never been reported when Same has been taken by mouth or intramuscularly. In fact, SAMe is very beneficial in PD L-Dopa, used to treat PD, depletes SAMe worsening depression and other symptoms

SAMe for Depression in Parkinson’s 12-wk DBRPC SAMe 1200-2400 mg/d vs citalopram10-20 mg/d 17 men + 15 women Baseline 12 weeks HAMD-17 Motor Sxs HAMD-17 Motor Sxs SAMe 18 25 11 15 Citalopram 18 24 8 26 Placebo 18 24 15 26 Both improved depression. SAMe also improved motor symptoms. (Varanese S, Brown RP, Di Rocco A, et al. Safety and preliminary evaluation of SAM-e and escitalopram in treatment of depression associated with PD. Longone Medical Center, NYU. Poster presentation, 2010.)

Cognitive Function in Adults without Dementia Nutritional Formula (NF) Folic acid 400mcg, B12 6mcg, Vit E 30 IU, SAMe 400mg, N-acetyl cysteine 600 mg, Acetyl-L-carnitine 500mg Cognitive Function in Adults without Dementia improved word recall in subjects <74 years old Early-stage Alzheimer’s improved Neuropsychiatric Inventory (NPI) - aggression, motor performance. Dementia Rating Scale improved 31% - Conceptualization, construction, attention, initiation/perseveration Moderate to Late Stage Alzheimer’s -Improved NPI and behavioral-psychiatric symptoms (Chan A. et al. J Nutr Health Aging. 2010; Chan A. et al. Am J Alzheimer’s Disease & other Dementia. 2009; Remington R. et al. Am J Alzheimer’s Disease & other Dementia. 2009.)

SAM-e Do Nots Do not break tablets or refrigerate Do not break blister pack seals until ready to use Do not use “bargain brands”

Mania in Bipolar Disorder SAMe Does NOT Cause Possible Side Effects of SAMe: activation, mild anxiety, nausea, loose stools Mania in Bipolar Disorder SAMe Does NOT Cause Weight gain Sexual dysfunction Loss of libido Sedation Mental clouding

Key References Bottiglieri T. Folate, Vitamin B12 and S-adenosylmethionine. Psychiatric Clinics of North America. Mar 2013 36(1):1-14. Brown RP, Gerbarg PL, Muskin PR. How to Use Herbs, Nutrients, and Yoga in Mental Health Care. W.W. Norton & Company, New York. 2009. Brown RP and Gerbarg PL. Chapter 38. Complementary and Integrative Treatments in Brain Injury in Textbook of Traumatic Brain Injury, Second Edition, ed by Silver JM, McAllister TW, and Yudofsky SC, American Psychiatric Press, Inc. Washington, DC, 2011. Pp. 599-622.

Additional References Chan A. et al. A vitamin/nutriceutical formulation improves memory and cognitive performance in community-dwelling adults without dementia.J Nutr Health Aging.2010;14(3):224-30. Chan A. et al. Efficacy of a vitamin/nutriceutical formulation for early-stage Alzheimer’s: 1 year, open-label pilot study. Am J Alzheimer’s Disease & other Dementia. 2009;23(6):571-589. Remington R. et al. Efficacy of a vitamin/nutriceutical formulation for moderate-stage to later-stage Alzheimer’s: Placebo-controlled pilot study. Am J Alzheimer’s Disease & other Dementia.2009;24(1):27- 33.